Osteoporosis is a disease leading to excessive breakdown of bone substance and structure culminating in increased susceptibility to fracture. It is a common pathological condition in elderly people where it is associated with a high incidence of morbidity and pain, and in some cases permanent immobilization.
Osteoporotic bone breaks under minimal trauma and resulting fractures are difficult to treat. Bone fractures associated with osteoporosis occur mainly in the femoral neck, in the wrist, and in vertebrae. For example, vertebral compression fractures are common, the vast majority of which are associated with intense pain at the site of the fracture which may become chronic. Lung problems and loss of mobility are some general consequences of vertebral compression fractures and can be permanent in the elderly, often leading to death through secondary disorders (e.g. pneumonia or pulmonary embolism). There are approximately 20,000 hip fractures per year in Australians aged over 60 years (increasing by 40% each decade), and approximately 25% of those who sustain a hip fracture die within 12 months post-fracture (Osteoporosis Australia, (2007), “The Burden of Brittle Bones”, White paper). Furthermore, of those who do not die following hip fracture, approximately 50% will suffer some level of dependence in their basic daily activities (such as toileting, grooming, etc.) representing a significant burden and health cost (Osteoporosis Australia (2007), “The Burden of Brittle Bones”, White paper; Berry et al. (2007), “Second hip fracture in older men and women: the Framingham Study”, Arch Intern Med.; 167:1971-6).
While the incidence of bone fracture in the elderly is generally increasing, therapeutic choices are limited. Currently, antiresorptives (e.g. bisphosphonates, denosumab, hormone therapy) are the most commonly used treatments for osteoporosis. These agents are designed to slow bone remodelling and increase bone density. However, they have been associated with significant side effects including osteonecrosis of the jaw, atypical fractures, atrial fibrillation, and increased risk of stroke or cancer. Anabolic agents may be used to generate new bone in patients with osteoporosis. However, finding anabolic factors that increase bone mass and regulate the balance between bone and fat has been challenging. In addition, the only commercially available anabolic agent (teriparatide) is not only very expensive and difficult to administer but is also associated with side effects including lowered blood pressure, nausea, pain, weakness, and depression. Moreover, the use of teriparatide in rats has been found to cause malignant tumour growth (osteogenic carcinoma). In general, therapeutic choices for osteoporosis are limited and the development of new therapeutic approaches that stimulate bone formation is a priority.
There is a need for alternative methods and compositions for the treatment of osteoporosis and related disorders.